The impact of neutrophil-to-lymphocyte ratio on staging and mortality risk stratification of cardiovascular-kidney-metabolic syndrome

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic disorder involving pathophysiological interactions among metabolic risk factors, renal system, and cardiovascular system, with consequent systemic inflammatory and oxidative stress responses. Neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic indicator of systemic inflammation and immunity, but its mortality predictive value in CKM syndrome has not been investigated. METHODS: Totally 19,525 participants were included from NHANES database (1999-2018), and were divided into 4 groups by their NLR level (quartile 1 to 4). Study outcomes were all-cause and cardiovascular mortality. Binary and ordinal logistic regression was used to investigate the relationship between NLR and CKM stages, and cox regression model and restricted cubic spline (RCS) were used to assessed the association between the NLR and outcomes. Subgroup analysis was conducted to investigate the risk in different CKM stage. RESULTS: During the median follow-up of 9.2 years, 10.93% patients (n = 2,926) died, of which 3.35% patients (n = 944) died from cardiovascular disease. Compared to patients with NLR in quartile 1 (as reference), elevated NLR quartiles were associated with a higher prevalence of advanced CKM stage. After adjustment, compared to NLR in quartile 1, the hazard radio of cardiovascular mortality was 1.46 ([95%CI 1.03-2.06], P = 0.035) for quartile 2, 1.45 ([95%CI 1.04-2.03], P = 0.030) for quartile 3, and 1.95 ([95%CI 1.41-2.70], P < 0.001) for quartile 4. RCS analysis also showed a linear association between NLR and cardiovascular mortality (P for nonlinearity = 0.722). For patients at advanced CKM stage, elevated NLR level was significantly associated with increased risk of mortality compared with those at early CKM stage. CONCLUSION: This study finds that higher NLR level is associated with increased risk of mortality, and NLR serves as an independent predictor of advanced CKM stages, indicating that NLR can be used as a risk stratification tool for different CKM stages. CLINICAL TRIAL NUMBER: Not applicable.